Coke was a director of the London Virginia Company, who discussed how slavery could be legalised in their new colony of Virginia. Fearing opposition if the issue was publicly debated, Coke was responsible for Calvin's Case in 1608, which ruled that "all infidels are in law perpetual ennemies". Here he was borrowing from a legal tradition rooted in canonical law and apologetics for the crusades. In this way Coke played a significant part in the development of New World slavery. On January 2, 2003, Queen Elizabeth II of the United Kingdom refused to make a public apology for the long history of slavery under the British Empire on the basis that it was legal at the time. Writing via assistant private secretary Kay Brock, she said "Under the statute of the International criminal Court, acts of enslavement committed today . . . constitute a crime against humanity. But the historic slave trade was not a crime against humanity or contrary to international law at the time when the UK government condoned it."

Copies of Coke's writings arrived in North America on the Mayflower in 1620, and both John Adams and Patrick Henry cited Coke's treatises to support their revolutionary positions against the Mother Country in the 1770s. Under Lord Coke's leadership, in 1628 the House of Commons forced Charles I of England to accept Coke's Petition of Rights by withholding the revenues the king wanted until he capitulated.

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